1. Field of the Invention
The present invention relates to new crystalline forms of carvedilol and pharmaceutical compositions thereof, as well as processes for its preparation and manufacture.
2. Description of the Related Art
Carvedilol, 1-(Carbazol-4-yloxy-3-[[2-(o-methoxyphenoxy)ethyl]amino]-2-propanol (CAS Registry No. 72956-09-3), has the formula as given below:

Carvedilol as a free base is used for treatment of hypertension, congestive heart failure and angina. The currently commercially available carvedilol product is a conventional, tablet prescribed as a twice-a-day medication.
U.S. Pat. No. 4,503,067 discloses carbazolyl-(4)-oxypropanolamine compounds and salts thereof with pharmacologically acceptable acids. The patent discloses the conversion of carbazolyl-(4)-oxypropanolamine compounds into their pharmacologically acceptable salts, by reacting with an equivalent amount of an inorganic or organic acid such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulphuric acid, acetic acid, citric acid, maleic acid or benzoic acid in an organic solvent.
International Application publication number WO 2004/002419 discloses and designates the following forms of carvedilol, pharmaceutical compositions thereof and methods of using the same to treat cardiovascular diseases including hypertension, congestive heart failure and angina:
Carvedilol dihydrogen phosphate hemihydrateForm-ICarvedilol dihydrogen phosphate dihydrateForm-IICarvedilol dihydrogen phosphate methanol solvateForm-IIICarvedilol dihydrogen phosphate dihydrateForm-IVCarvedilol dihydrogen phosphateForm-VCarvedilol hydrogen phosphateForm-VI
The WO 2004/002419 application further characterizes (XRD, thermal analysis, FT-Raman spectrums) crystalline forms of carvedilol phosphate salt. The processes disclosed for preparation of carvedilol dihydrogen phosphate hemihydrate (Form-I) involve the addition of phosphoric acid to the solution of carvedilol in acetone-water, followed by isolation and drying under vacuum. The processes disclosed for preparation of carvedilol dihydrogen phosphate dihydrate involve the slurrying of the Form-I with an acetone/water mixture between 10 and 30° C. for several days, and for the preparation of carvedilol dihydrogen phosphate methanol solvate (Form-III) by slurring Form-I in methanol between 10 and 30° C. for several days. The application further discloses that the carvedilol dihydrogen phosphate displays higher solubility when compared to the free base of carvedilol.
International Application publication number WO 2005/051383 discloses several crystalline carvedilol salts selected from mandelate, lactate, maleate, sulfate, glutarate, mesylate, phosphate, citrate, hydrobromide, oxalate, hydrochloride, benzoate as solvates and anhydrous forms. The application further discloses pharmaceutical compositions containing the above salts, anhydrous forms or solvates thereof, and methods of using the compound in the treatment of certain disease in mammals.
It has now been shown that a novel crystalline form of carvedilol phosphate (i.e., carvedilol dihydrogen phosphate salt) can be isolated as pure crystalline, sesquihydrate, which is found to be more stable.